AUTHOR=van de Merbel Arjanneke F. , van der Mark Maaike H. , Aalders Tilly , Puhr Martin , Mehra Niven , Schalken Jack , van der Horst Geertje , van der Pluijm Gabri 

TITLE=Anti-neoplastic effects of the antipsychotic drug penfluridol in preclinical prostate cancer models

JOURNAL=Frontiers in Oncology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1685758

DOI=10.3389/fonc.2025.1685758

ISSN=2234-943X

ABSTRACT=IntroductionThe development of therapy resistance and the formation of distant metastases represent clinical unmet needs for patients with advanced prostate cancer (PCa). The use of drugs for other indications, i.e. drug repurposing, shows great promise for cancer treatment. Drug repurposing could allow new cancer treatments to be introduced relatively quickly and at lower costs. Penfluridol, an approved antipsychotic drug, has strong cytolytic effects in multiple cancers.MethodsIn this study, we have investigated the potential anti-tumor effects of penfluridol in preclinical and ‘near-patient’ PCa models.ResultsPenfluridol significantly reduced the viability of a panel of human PCa cells, induced apoptosis by increasing caspase-3/7 levels and decreased the number of PCa stem cells in vitro. Penfluridol reduced the viability and induced cytotoxic effects in three-dimensional cultures and in ex vivo cultured PCa tissue slices (patient-derived xenograft, freshly isolated PCa biopsies). Moreover, penfluridol significantly reduced the viability of docetaxel-resistant PCa cells and exerted synergistic effects in combination with docetaxel in docetaxel-resistant PCa.DiscussionIn conclusion, penfluridol exhibited cytotoxic effects in multiple preclinical PCa models. Further research is warranted to address the translational value of our findings.